Introduction: Hypothyroidism is one of the most common endocrine diseases, with an incidence of 2-10% in different populations. The purpose of this study was to investigate the effectiveness of acceptance and commitment therapy on the anxiety, depression psychological well-being of patients with hypothyroidism. Materials and Methods: This quasi-experimental clinical trial study was performed on thirty women with hypothyroidism, who were selected using the purposive sampling method and randomly assigned in two groups, the intervention and controls (n=15 each). Data were collected using the Beck Anxiety inventory (BAI) Beck depression inventory (BDI) and psychological well-being Reef. Data analysis was done by SPSS-21 software and using the repeated measures ANOVA and Benferroni post hoc test. Results: Results of the repeated measure of variance analysis showed a significant difference between the performance of the experimental and control groups in anxiety (P=0.001, F=14.16) depression (P=0.001, F=13.12) and psychological well-being (P=0.001, F=26.60) in the post-test stage and after three months of follow-up. Conclusion: Findings indicate the effectiveness of ACT therapy on the anxiety, depression and psycholgical well-being of patients with hypothyroidism; confirming that this intervention can be used as a complementary treatment, along with medication, to improve the quality of life of these individuals.